CN103351390A - 用于治疗肺部和心血管病症的联芳基pde4 抑制剂 - Google Patents
用于治疗肺部和心血管病症的联芳基pde4 抑制剂 Download PDFInfo
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- CN103351390A CN103351390A CN201310270697XA CN201310270697A CN103351390A CN 103351390 A CN103351390 A CN 103351390A CN 201310270697X A CN201310270697X A CN 201310270697XA CN 201310270697 A CN201310270697 A CN 201310270697A CN 103351390 A CN103351390 A CN 103351390A
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
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- C07—ORGANIC CHEMISTRY
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/84—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116265440A (zh) * | 2021-12-16 | 2023-06-20 | 贵州大学 | 一种水杨酮拼接吡啶酮类化合物及其制备方法及应用 |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
CA2722582A1 (en) * | 2007-11-21 | 2009-05-28 | Decode Genetics Ehf. | Biaryl pde4 inhibitors for treating inflammation |
CN103351390A (zh) | 2007-11-21 | 2013-10-16 | 解码遗传Ehf公司 | 用于治疗肺部和心血管病症的联芳基pde4 抑制剂 |
WO2010059838A2 (en) * | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Pde4 inhibitors selective for the long form of pde4 for treating inflammation and avoiding side effects |
CA2804593C (en) | 2010-07-09 | 2015-11-24 | Pfizer Limited | Biphenyloxybenzensulphonamide derivatives useful as sodium channel inhibitors |
CA2801032A1 (en) | 2010-07-12 | 2012-01-19 | Pfizer Limited | N-sulfonylbenzamide derivatives useful as voltage gated sodium channel inhibitors |
US9096500B2 (en) | 2010-07-12 | 2015-08-04 | Pfizer Limited | Acyl sulfonamide compounds |
CA2804351A1 (en) | 2010-07-12 | 2012-01-19 | Pfizer Limited | Chemical compounds |
WO2012007883A1 (en) * | 2010-07-12 | 2012-01-19 | Pfizer Limited | Sulfonamide derivatives as nav1.7 inhibitors for the treatment of pain |
EP2593431B1 (en) | 2010-07-12 | 2014-11-19 | Pfizer Limited | N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels |
US8865723B2 (en) | 2012-10-25 | 2014-10-21 | Tetra Discovery Partners Llc | Selective PDE4 B inhibition and improvement in cognition in subjects with brain injury |
US9073875B2 (en) | 2012-11-20 | 2015-07-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of indoleamine 2,3-dioxygenase |
CA2895209C (en) * | 2013-03-14 | 2022-07-19 | Venkataiah Bollu | Substituted pyridine and pyrazine compounds as pde4 inhibitors |
DK3033082T3 (da) | 2013-08-16 | 2021-09-20 | Univ Maastricht | Behandling af kognitiv svækkelse med pde4-hæmmer |
CA2921297A1 (en) * | 2013-08-16 | 2015-02-19 | Universiteit Maastricht | Treatment of cognitive impairment with combination therapy |
CN103588758A (zh) * | 2013-11-04 | 2014-02-19 | 南京大学 | 一类含1,4-苯并二噁烷骨架的硝基咪唑衍生物的合成、制备及其在抗癌药物中的应用 |
RS61013B1 (sr) | 2014-10-24 | 2020-11-30 | Landos Biopharma Inc | Terapeutski preparati zasnovani na lantionin sintetazi c- sličnom proteinu-2 |
UY36705A (es) * | 2015-06-03 | 2016-11-30 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos de 4-hidroxi-3-(heteroaril)piridin-2-ona como agonistas de apj |
WO2017089347A1 (en) | 2015-11-25 | 2017-06-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of braf inhibitor resistant melanomas |
DE102016205102B4 (de) * | 2015-12-17 | 2022-01-05 | Robert Bosch Gmbh | Ventil in einer Hochdruckpumpe eines Kraftstoffeinspritzsystems und Hochdruckpumpe eines Kraftstoffeinspritzsystems mit diesem Ventil |
AU2018374767A1 (en) | 2017-11-30 | 2020-06-25 | Landos Biopharma, Inc. | Therapies with lanthionine C-like protein 2 ligands and cells prepared therewith |
WO2019119207A1 (en) * | 2017-12-18 | 2019-06-27 | Merck Sharp & Dohme Corp. | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
CN110194743B (zh) * | 2018-02-26 | 2022-11-11 | 云南大学 | 苯基(3-甲氧基-4-(4-甲基-1h-咪唑-1-基)苯基)甲酮类化合物 |
CN110194746B (zh) * | 2018-02-26 | 2022-11-18 | 云南大学 | 用于治疗阿尔茨海默症的化合物,其制备方法和用途 |
CN110194744B (zh) * | 2018-02-26 | 2022-11-11 | 云南大学 | 一种抑制β-淀粉样蛋白生成的化合物及其制备方法和用途 |
US11225483B2 (en) | 2018-03-07 | 2022-01-18 | Northwestern University | Substituted fused pyrrolo-diazepinones and uses thereof |
US11117881B2 (en) | 2019-12-20 | 2021-09-14 | Landos Biopharma, Inc. | Lanthionine c-like protein 2 ligands, cells prepared therewith, and therapies using same |
CN114057589B (zh) * | 2020-08-07 | 2025-05-23 | 上海再极医药科技有限公司 | 18f标记的联苯类化合物、其中间体、制备方法、药物组合物及应用 |
JP2023542908A (ja) | 2020-09-18 | 2023-10-12 | シャンハイ ファーマシューティカルズ ホールディング カンパニー,リミティド | カルボニル複素環系化合物及びその使用 |
JP2024502083A (ja) * | 2020-12-31 | 2024-01-17 | 清華大学 | ピリジン-2-アミン誘導体、その医薬組成物、及び使用 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5773462A (en) * | 1995-06-23 | 1998-06-30 | Medichem Research, Inc. | Biflavanoids and derivatives thereof as antiviral agents |
US6221604B1 (en) * | 2000-02-07 | 2001-04-24 | Pe Corporation | Electron-deficient nitrogen heterocycle-substituted fluorescein dyes |
EP1227086A1 (en) * | 1999-10-22 | 2002-07-31 | Takeda Chemical Industries, Ltd. | 1-substituted phenyl-1-(1h-imidazol-4-yl) alcohols, process for producing the same and use thereof |
JP3582936B2 (ja) * | 1996-07-10 | 2004-10-27 | 株式会社ノエビア | 皮膚外用剤 |
WO2004093799A2 (en) * | 2003-04-18 | 2004-11-04 | Bristol-Myers Squibb Company | Thyroid receptor ligands |
CN1551769A (zh) * | 2000-12-20 | 2004-12-01 | 被取代的8-芳基喹啉磷酸二酯酶-4抑制剂 | |
CN1882327A (zh) * | 2003-11-19 | 2006-12-20 | 症变治疗公司 | 含磷的新的拟甲状腺素药 |
Family Cites Families (118)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2535015A (en) * | 1948-06-19 | 1950-12-19 | Dow Chemical Co | Diphenol compound composition for coccidiosis control |
US3144479A (en) * | 1958-08-07 | 1964-08-11 | Chemie Linz Ag | New iodine-containing benzoic acid esters |
US4287366A (en) * | 1980-03-10 | 1981-09-01 | Mitsui Toatsu Chemicals, Inc. | Process for preparing bisphenol sulfone derivatives |
LU86387A1 (fr) * | 1986-04-04 | 1987-12-07 | Oreal | Composes aromatiques,leur procede de preparation et leur utilisation en medicine humaine et veterinaire et en cosmetique |
EP0249963B1 (en) | 1986-06-20 | 1992-04-22 | Idemitsu Kosan Company Limited | Polycarbonates |
WO1988001165A1 (en) | 1986-08-11 | 1988-02-25 | Innovata Biomed Limited | Pharmaceutical formulations comprising microcapsules |
US5179079A (en) | 1986-12-16 | 1993-01-12 | Novo Nordisk A/S | Nasal formulation and intranasal administration therewith |
GB8723846D0 (en) | 1987-10-10 | 1987-11-11 | Danbiosyst Ltd | Bioadhesive microsphere drug delivery system |
IT1223343B (it) | 1987-11-03 | 1990-09-19 | Also Lab Sas | Formulazioni farmaceutiche per somministrazione transdermica |
US4994439A (en) | 1989-01-19 | 1991-02-19 | California Biotechnology Inc. | Transmembrane formulations for drug administration |
JPH05508616A (ja) | 1989-02-23 | 1993-12-02 | ローヌー プーラン ローラー インターナショナル(ホウルディングス)インコーポレイテッド | 治療用エアロゾル剤 |
GB8921222D0 (en) | 1989-09-20 | 1989-11-08 | Riker Laboratories Inc | Medicinal aerosol formulations |
US5292499A (en) | 1990-09-11 | 1994-03-08 | University Of Wales College Of Cardiff | Method of preparing medical aerosol formulations including drug dissolved in reverse micelles |
US5230884A (en) | 1990-09-11 | 1993-07-27 | University Of Wales College Of Cardiff | Aerosol formulations including proteins and peptides solubilized in reverse micelles and process for making the aerosol formulations |
GB9114760D0 (en) * | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
US5237062A (en) * | 1992-04-28 | 1993-08-17 | Hay Allan S | Polymers derived from phenolphthaleins |
JPH0624138A (ja) * | 1992-07-09 | 1994-02-01 | Hodogaya Chem Co Ltd | 感熱記録材料 |
US6632456B1 (en) | 1993-06-24 | 2003-10-14 | Astrazeneca Ab | Compositions for inhalation |
CA2144669A1 (en) | 1994-03-29 | 1995-09-30 | Kozo Akasaka | Biphenyl derivatives |
IL114950A0 (en) | 1994-08-22 | 1995-12-08 | Hoechst Schering Agrevo Gmbh | Biphenyl derivatives and herbicidal agentd containing the same |
US5707641A (en) | 1994-10-13 | 1998-01-13 | Pharmaderm Research & Development Ltd. | Formulations comprising therapeutically-active proteins or polypeptides |
US5594141A (en) * | 1994-11-23 | 1997-01-14 | Neurogen Corporation | Certain aminomethyl biphenyl, aminomethyl phenyl pyridine and aminomethyl phenyl pyrimidine derivatives; novel dopamine receptor subtype selective ligands |
EP0793662A1 (en) * | 1994-11-23 | 1997-09-10 | Neurogen Corporation | Aminomethyl aryl compounds; dopamine receptor subtype selective ligands |
AU704911B2 (en) * | 1994-11-24 | 1999-05-06 | Basilea Pharmaceutica Ag | Novel benzyl pyrimidines |
US6524557B1 (en) | 1994-12-22 | 2003-02-25 | Astrazeneca Ab | Aerosol formulations of peptides and proteins |
CH689139A5 (de) | 1995-04-03 | 1998-10-30 | Cerbios Pharma Sa | Verfahren zur Herstellung einer liposomalen, in Wasser dispergierbaren, oral zu verabreichenden, festen, trockenen therapeutischen Formulierung. |
US6309671B1 (en) | 1995-04-14 | 2001-10-30 | Inhale Therapeutic Systems | Stable glassy state powder formulations |
US5635161A (en) | 1995-06-07 | 1997-06-03 | Abbott Laboratories | Aerosol drug formulations containing vegetable oils |
WO1997003967A1 (en) | 1995-07-22 | 1997-02-06 | Rhone-Poulenc Rorer Limited | Substituted aromatic compounds and their pharmaceutical use |
US6120794A (en) | 1995-09-26 | 2000-09-19 | University Of Pittsburgh | Emulsion and micellar formulations for the delivery of biologically active substances to cells |
EP0801557B1 (en) | 1995-10-12 | 2003-07-02 | Supergen, Inc. | Liposome formulations of 5beta steroids |
DE19541146A1 (de) * | 1995-10-25 | 1997-04-30 | Schering Ag | Imidazolderivate und deren Verwendung als Stickstoffmonoxid-Synthase-Inhibitoren |
GB9604926D0 (en) * | 1996-03-08 | 1996-05-08 | Sandoz Ltd | Organic compounds |
AU708053B2 (en) * | 1996-03-29 | 1999-07-29 | Duphar International Research B.V. | Piperazine and piperidine compounds |
FR2754260B1 (fr) * | 1996-10-04 | 1998-10-30 | Adir | Nouveaux derives substitues de biphenyle ou de phenylpyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2753706B1 (fr) * | 1996-09-20 | 1998-10-30 | Nouvelles amines cycliques n-substituees, leur procede de preparation et les compositions pharmaceutiques les renfermant | |
TW486475B (en) * | 1996-12-26 | 2002-05-11 | Ube Industries | Acid addition salt of optically active piperidine compound and process for preparing the same |
FR2762514B1 (fr) * | 1997-04-29 | 1999-10-22 | Sanofi Sa | Utilisation de derives de la tetrahydropyridine pour la preparation de medicaments pour le traitement des maladies entrainant une demyelinisation |
EP0894794A1 (en) * | 1997-07-31 | 1999-02-03 | AESCULAPIUS FARMACEUTICI S.r.l. | Optical isomers of cloperastine |
AU1504599A (en) * | 1997-12-17 | 1999-07-05 | Shionogi & Co., Ltd. | Novel pyridine compounds |
WO1999059550A1 (en) | 1998-05-20 | 1999-11-25 | The Liposome Company, Inc. | Novel particulate formulations |
US6451349B1 (en) | 1998-08-19 | 2002-09-17 | Quadrant Healthcare (Uk) Limited | Spray-drying process for the preparation of microparticles |
GB9814172D0 (en) | 1998-06-30 | 1998-08-26 | Andaris Ltd | Formulation for inhalation |
AUPP494798A0 (en) | 1998-07-29 | 1998-08-20 | Pacific Biolink Pty Limited | Protective protein formulation |
AU757052B2 (en) * | 1998-09-09 | 2003-01-30 | Dart Neuroscience (Cayman) Ltd | Substituted gamma-phenyl-delta-lactones and analogs thereof and uses related thereto |
US6290987B1 (en) | 1998-09-27 | 2001-09-18 | Generex Pharmaceuticals, Inc. | Mixed liposome pharmaceutical formulation with amphiphiles and phospholipids |
US6294153B1 (en) | 1998-12-21 | 2001-09-25 | Generex Pharmaceuticals, Inc. | Aerosol pharmaceutical formulation for pulmonary and nasal delivery |
EP1338272A1 (en) | 1998-12-21 | 2003-08-27 | Generex Pharmaceuticals Inc. | Aerosol formulations for buccal and pulmonary application comprising chenodeoxycholate or deoxycholate |
US6436367B1 (en) | 1998-12-21 | 2002-08-20 | Generex Pharmaceuticals Inc. | Aerosol formulations for buccal and pulmonary application |
DE60021059T2 (de) | 1999-02-03 | 2006-05-18 | Powderject Research Ltd. | Partikuläre pharmazeutische Zusammensetzung für eine transdermale Partikelabgabe aus einem nadellosen Spritzensystem |
WO2000047203A1 (en) | 1999-02-12 | 2000-08-17 | Mqs, Inc. | Formulation and system for intra-oral delivery of pharmaceutical agents |
JP2002538195A (ja) | 1999-03-08 | 2002-11-12 | パウダージェクト リサーチ リミテッド | 生物活性化合物の持続放出用の無針注射器を使用する微粒子製剤の送達 |
AU3957400A (en) | 1999-04-16 | 2000-11-02 | Novo Nordisk A/S | Dry, mouldable drug formulation |
EP1187639A1 (en) | 1999-06-04 | 2002-03-20 | Delrx Pharmaceutical Corporation | Formulations comprising dehydrated particles of pharmaceutical agents and process for preparing the same |
JP2003507410A (ja) | 1999-08-25 | 2003-02-25 | アドバンスト インハレーション リサーチ,インコーポレイテッド | 乾燥粉末製剤からの放出調節 |
US20010036481A1 (en) | 1999-08-25 | 2001-11-01 | Advanced Inhalation Research, Inc. | Modulation of release from dry powder formulations |
MXPA02002257A (es) | 1999-08-31 | 2002-09-30 | Maxia Pharmaceuticals Inc | Bencilideno-tiazolidinadionas y analogos y su uso en el tratamiento de la diabetes. |
WO2001052894A2 (en) | 2000-01-20 | 2001-07-26 | Basilea Pharmaceutica Ag | Nasally administrable cyclic peptide compositions |
EP1129705A1 (en) | 2000-02-17 | 2001-09-05 | Rijksuniversiteit te Groningen | Powder formulation for inhalation |
US20050070578A1 (en) * | 2000-03-30 | 2005-03-31 | Baxter Anthony David | Small organic molecule regulators of cell proliferation |
PE20011227A1 (es) | 2000-04-17 | 2002-01-07 | Chiesi Farma Spa | Formulaciones farmaceuticas para inhaladores de polvo seco en la forma de aglomerados duros |
CA2406206C (en) | 2000-04-17 | 2012-03-20 | Vectura Limited | Improvements in or relating to formulations for use in inhaler devices |
GB0009468D0 (en) | 2000-04-17 | 2000-06-07 | Vectura Ltd | Improvements in or relating to formulations for use in inhaler devices |
US20020155084A1 (en) | 2000-06-02 | 2002-10-24 | The Regents Of The University Of The Michigan | Nanoemulsion formulations |
WO2002019989A2 (en) | 2000-09-08 | 2002-03-14 | Powderject Research Limited | Alginate particle formulation |
FI20002768L (fi) | 2000-12-18 | 2002-06-19 | Licentia Oy | Enteropäällysteisiä lääkekoostumuksia ja niiden valmistus |
US7153875B2 (en) | 2001-03-07 | 2006-12-26 | Incyte San Diego | Heterocyclic derivatives for the treatment of cancer and other proliferative diseases |
GB0107106D0 (en) | 2001-03-21 | 2001-05-09 | Boehringer Ingelheim Pharma | Powder inhaler formulations |
EP1373257B9 (en) * | 2001-03-29 | 2008-10-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
US20030019437A1 (en) | 2001-07-26 | 2003-01-30 | John Fore | Ungulate game animal feed system and method |
ATE395042T1 (de) | 2001-08-16 | 2008-05-15 | Baxter Int | Darreichungsformen welche mikropartikel und treibgas enthalten |
EP1456178A1 (en) * | 2001-12-21 | 2004-09-15 | Smithkline Beecham Plc | 7-sulfonyl-3-benzazepine derivatives as modulators of the dopamine receptor and their use for the treatment of cns disorders |
AU2003215334A1 (en) | 2002-02-22 | 2003-09-09 | Advanced Inhalation Research, Inc. | Inhalable formulations for sustained release |
GB0205256D0 (en) * | 2002-03-06 | 2002-04-17 | Oxford Glycosciences Uk Ltd | Novel compounds |
AU2003230689B2 (en) | 2002-03-20 | 2006-06-29 | Alkermes, Inc. | Inhalable sustained therapeutic formulations |
DE60335359D1 (de) * | 2002-04-30 | 2011-01-27 | Kudos Pharm Ltd | Phthalazinonderivate |
JP2006502972A (ja) | 2002-05-07 | 2006-01-26 | フェリング ベスローテン フェンノートシャップ | デスモプレシンの口腔内分散性医薬製剤 |
AU2003225305A1 (en) * | 2002-05-08 | 2003-11-11 | Bristol-Myers Squibb Company | Pyridine-based thyroid receptor ligands |
AU2003281040A1 (en) * | 2002-07-10 | 2004-02-02 | Sumitomo Pharmaceuticals Co., Ltd. | Biaryl derivatives |
DK1581535T5 (da) * | 2003-01-09 | 2009-12-21 | Astellas Pharma Inc | Pyrrolopyridazinderivater |
EP1980560B1 (en) * | 2003-03-14 | 2011-05-25 | Astellas Pharma Inc. | C-glycoside derivatives for the treatment of diabetes |
CA2519677A1 (en) | 2003-03-24 | 2004-10-07 | Merck & Co., Inc. | Biaryl substituted 6-membered heterocycles as sodium channel blockers |
CA2520804A1 (en) | 2003-04-03 | 2004-10-28 | Merck & Co., Inc. | Biaryl substituted pyrazoles as sodium channel blockers |
EP1694654B1 (en) | 2003-11-10 | 2011-03-02 | Merck Sharp & Dohme Corp. | Substituted triazoles as sodium channel blockers |
EP1697339A1 (en) * | 2003-12-25 | 2006-09-06 | Takeda Pharmaceutical Company Limited | 3-(4-benzyloxyphenyl)propanoic acid derivatives |
EP1737809B1 (en) * | 2004-02-27 | 2013-09-18 | Amgen, Inc | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
CA2557372C (en) * | 2004-03-05 | 2013-01-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 antagonists |
EP1726580A4 (en) * | 2004-03-15 | 2008-02-13 | Takeda Pharmaceutical | AMINOPHNYLPROPANO ACID DERIVATIVE |
UY29016A1 (es) | 2004-07-20 | 2006-02-24 | Boehringer Ingelheim Int | Analogos de dipeptidos inhibidores de la hepatitis c |
US7465726B2 (en) * | 2004-08-02 | 2008-12-16 | Osi Pharmaceuticals, Inc. | Substituted pyrrolo[2.3-B]pyridines |
CN100371324C (zh) | 2004-09-07 | 2008-02-27 | 天津大学 | 二烷基、二芳基四取代杂环化合物、其制备方法及其应用 |
AP2007003980A0 (en) * | 2004-11-23 | 2007-06-30 | Pfizer Prod Inc | Dibenzylamine compounds and derivatives |
BRPI0517500B8 (pt) | 2004-12-23 | 2021-05-25 | Galderma Res & Dev | composto, uso de uma composição, composição farmacêutica, composição cosmética, usos não-terapêuticos de uma composição cosmética e processo cosmético para melhorar a aparência da pele |
KR20070107022A (ko) | 2005-01-07 | 2007-11-06 | 신타 파마슈티칼스 코프. | 염증 및 면역 관련 용도를 위한 화합물 |
WO2006128056A2 (en) | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphinic acid-containing thyromimetics |
JP2007063225A (ja) * | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
US7723336B2 (en) * | 2005-09-22 | 2010-05-25 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
US20070078136A1 (en) * | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
EP1931797A2 (en) * | 2005-09-29 | 2008-06-18 | Bayer HealthCare AG | Pde inhibitors and combinations thereof for the treatment of urological disorders |
WO2007067537A1 (en) * | 2005-12-07 | 2007-06-14 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine kinase inhibiting compounds |
EP1960377A1 (en) * | 2005-12-08 | 2008-08-27 | Novartis AG | l , l , 3-TRI0X0-l , 2 , 5-THIADIAZ0LIDINES AND THEIR USE AS PTP-ASES INHIBITORS |
NZ568904A (en) | 2005-12-30 | 2011-05-27 | Merck Sharp & Dohme | 1,3-oxazolidin-2-one derivatives useful as CETP inhibitors |
WO2007123953A2 (en) * | 2006-04-19 | 2007-11-01 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
TW200815377A (en) | 2006-04-24 | 2008-04-01 | Astellas Pharma Inc | Oxadiazolidinedione compound |
US8148417B2 (en) * | 2006-05-18 | 2012-04-03 | Arena Pharmaceuticals, Inc. | Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto |
EP2076503B1 (en) * | 2006-05-19 | 2013-07-17 | Taisho Pharmaceutical Co., Ltd | C-phenyl glycitol compound for the treatment of diabetes |
KR20090025367A (ko) * | 2006-06-28 | 2009-03-10 | 가부시키가이샤산와카가쿠켄큐쇼 | 신규 6-5계 이환식 복소환 유도체 및 그 의약용도 |
CN101522614B (zh) * | 2006-08-09 | 2014-06-25 | 史密丝克莱恩比彻姆公司 | 作为阿片样物质受体的拮抗剂或反向激动剂的化合物 |
JP5231829B2 (ja) | 2007-02-15 | 2013-07-10 | 石原産業株式会社 | ピリジル−トリアゾロピリミジン誘導体又はその塩、それらを含有する有害生物防除剤並びにそれらの製造方法 |
EP2132197A2 (en) * | 2007-03-21 | 2009-12-16 | Almirall, S.A. | Substituted pyrimidines as adenosine receptor antagonists |
PE20090938A1 (es) * | 2007-08-16 | 2009-08-08 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de benceno sustituido con glucopiranosilo |
CN103351390A (zh) | 2007-11-21 | 2013-10-16 | 解码遗传Ehf公司 | 用于治疗肺部和心血管病症的联芳基pde4 抑制剂 |
CA2722582A1 (en) | 2007-11-21 | 2009-05-28 | Decode Genetics Ehf. | Biaryl pde4 inhibitors for treating inflammation |
AU2008326385B2 (en) * | 2007-11-21 | 2013-12-05 | Decode Genetics Ehf | Substituted benzoazole PDE4 inhibitors for treating inflammatory, cardiovascular and CNS disorders |
US8877816B2 (en) * | 2007-11-21 | 2014-11-04 | Decode Genetics Ehf | 4-(or 5-) substituted catechol derivatives |
FR2932180B1 (fr) | 2008-06-04 | 2012-08-10 | Centre Nat Rech Scient | Dihydro iso ca-4 et analogues : puissants cytotoxiques, inhibiteurs de la polymerisation de la tubuline |
WO2010059838A2 (en) | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Pde4 inhibitors selective for the long form of pde4 for treating inflammation and avoiding side effects |
WO2010059836A1 (en) | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Substituted aza-bridged bicyclics for cardiovascular and cns disease |
-
2008
- 2008-11-20 CN CN201310270697XA patent/CN103351390A/zh active Pending
- 2008-11-20 CN CN2008801251832A patent/CN102026970B/zh not_active Expired - Fee Related
- 2008-11-20 EP EP08852110A patent/EP2222639A1/en not_active Withdrawn
- 2008-11-20 AU AU2008326309A patent/AU2008326309C1/en not_active Ceased
- 2008-11-20 KR KR1020107013784A patent/KR20100098653A/ko not_active Ceased
- 2008-11-20 KR KR1020107013786A patent/KR20100108346A/ko not_active Ceased
- 2008-11-20 EP EP13000709.9A patent/EP2628727A3/en not_active Withdrawn
- 2008-11-20 WO PCT/US2008/084230 patent/WO2009067621A1/en active Application Filing
- 2008-11-20 EP EP13000717.2A patent/EP2674417A3/en not_active Withdrawn
- 2008-11-20 JP JP2010535073A patent/JP2011504505A/ja active Pending
- 2008-11-20 US US12/275,152 patent/US20090136473A1/en not_active Abandoned
- 2008-11-20 CA CA2722611A patent/CA2722611A1/en not_active Abandoned
- 2008-11-20 US US12/275,163 patent/US20090324569A1/en not_active Abandoned
-
2010
- 2010-05-20 IL IL205882A patent/IL205882A0/en unknown
-
2012
- 2012-03-26 US US13/430,164 patent/US8791267B2/en not_active Expired - Fee Related
- 2012-04-27 US US13/457,716 patent/US20120213758A1/en not_active Abandoned
-
2014
- 2014-03-10 JP JP2014046962A patent/JP2014185149A/ja not_active Withdrawn
- 2014-06-23 US US14/311,728 patent/US20140301999A1/en not_active Abandoned
- 2014-10-10 JP JP2014209336A patent/JP2015044829A/ja not_active Withdrawn
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5773462A (en) * | 1995-06-23 | 1998-06-30 | Medichem Research, Inc. | Biflavanoids and derivatives thereof as antiviral agents |
JP3582936B2 (ja) * | 1996-07-10 | 2004-10-27 | 株式会社ノエビア | 皮膚外用剤 |
EP1227086A1 (en) * | 1999-10-22 | 2002-07-31 | Takeda Chemical Industries, Ltd. | 1-substituted phenyl-1-(1h-imidazol-4-yl) alcohols, process for producing the same and use thereof |
US6221604B1 (en) * | 2000-02-07 | 2001-04-24 | Pe Corporation | Electron-deficient nitrogen heterocycle-substituted fluorescein dyes |
CN1551769A (zh) * | 2000-12-20 | 2004-12-01 | 被取代的8-芳基喹啉磷酸二酯酶-4抑制剂 | |
WO2004093799A2 (en) * | 2003-04-18 | 2004-11-04 | Bristol-Myers Squibb Company | Thyroid receptor ligands |
CN1882327A (zh) * | 2003-11-19 | 2006-12-20 | 症变治疗公司 | 含磷的新的拟甲状腺素药 |
Non-Patent Citations (2)
Title |
---|
GIUSEPPE CAPOZZI 等: "Electrophilic Substitution of Phenols with α,α’-Dioxothiones and ortho-Thioquinones", 《EUR. J. ORG. CHEM.》 * |
L.D.SMIRNOV 等: "Synthesis and study of some electrophilic reactions of 2-phenyl-3-hydroxypyridine N-oxides", 《IZVESTIYA AKADEMII NAUK SSSR, SERIYA KHIMICHESKAYA》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116265440A (zh) * | 2021-12-16 | 2023-06-20 | 贵州大学 | 一种水杨酮拼接吡啶酮类化合物及其制备方法及应用 |
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KR20100108346A (ko) | 2010-10-06 |
EP2628727A3 (en) | 2013-12-25 |
KR20100098653A (ko) | 2010-09-08 |
US20140301999A1 (en) | 2014-10-09 |
AU2008326309B2 (en) | 2014-10-02 |
US20120213758A1 (en) | 2012-08-23 |
CN102026970B (zh) | 2013-07-31 |
JP2014185149A (ja) | 2014-10-02 |
AU2008326309A1 (en) | 2009-05-28 |
EP2674417A2 (en) | 2013-12-18 |
JP2011504505A (ja) | 2011-02-10 |
CN102026970A (zh) | 2011-04-20 |
US20090324569A1 (en) | 2009-12-31 |
CA2722611A1 (en) | 2009-05-28 |
EP2674417A3 (en) | 2014-04-09 |
EP2628727A2 (en) | 2013-08-21 |
AU2008326309C1 (en) | 2015-03-12 |
JP2015044829A (ja) | 2015-03-12 |
US20090136473A1 (en) | 2009-05-28 |
WO2009067621A1 (en) | 2009-05-28 |
EP2222639A1 (en) | 2010-09-01 |
US8791267B2 (en) | 2014-07-29 |
US20120183522A1 (en) | 2012-07-19 |
IL205882A0 (en) | 2010-11-30 |
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